SUBCONJUNCTIVAL INJECTIONS OF MYELOID-DERIVED SUPPRESSOR CELLS TO PREVENT GRAFT REJECTION IN KERATOPLASTY

Myeloid-derived suppressor cells (MDSCs) play an important role in the cellular network regulating immune responses in cancer, autoimmunity, and organ transplantation. Herein, we evaluated the immunosuppressive effect of local injected MDSCs on corneal allograft.

corneal transplantation murine model

MDSCs were administrated via subconjunctival injection twice on days 0 and 7 after keratoplasty. A corneal transplantation was established using C57BL/6 and BALB/c mice, and graft corneal opacity was measured to evaluate graft rejection. Corneal neovascularization and inflammatory cell infiltration were detected by immunohistochemistry. The proportion of CD4+ T cells and dendritic cells in the draining lymph nodes (DLNs) was examined by flow cytometry.

Graft survival in the MDSCs treated mice were increased after 6 weeks. Local MDSC inhibited the maturation of antigen presenting cells and the proliferation of Th1 CD4+ in draining lymph nodes (LNs). Control mice presented prominent neovascular and lymphatic vessels into the grafted corneas.  MDSCs administration showed prominent anti-angiogenic/anti-lymphangiogenic effects. 

Subconjunctival Injections of MDSCs can suppress graft rejection through inhibiting both neovascularization of grafted corneas and Th1 CD4+cells into the corneas. Thus, local injected MDSCs showed therapeutic potentials to prevent corneal graft rejection.